Experiments are proposed for determining the effects of heavy metal ions on synaptic transmission in the isolated frog sciatic nerve-sartorius muscle preparation. Such studies should improve our understanding of the effects of these toxic metals on the nervous system and provide basic data concerning the role of polyvalent cations in synaptic transmission. Both the presynaptic and postsynaptic effects of these ions will be examined as they are manifested in intracellular microelectrode recordings from motor endplates. Presynaptic effects will be determined by measurements of (1) frequency of miniature endplate potentials, (2) quantal content of the endplate potential, and (3) time course and magnitude of facilitation. Postsynaptic effects will be revealed by measurements of (1) the amplitude and time course of the endplate potential, (2) the input resistance of the muscle cell, (3) the mean amplitude of the miniature endplate potential, (4) the magnitude and time course of desensitization, (5) the height and time course of postsynaptic potentials produced by the iontophoresis of acetylcholine directly onto the endplate membrane and (6) the reversal potentials for the endplate potential and for the acetylcholine iontophoretic potential. Our published work has already shown that lead inhibits the phasic release and stimulates the spontaneous release of acetylcholine from motor nerve terminals. Work now in progress has enabled us to make the rather unexpected observation that the endplate potential is increased, rather than decreased, in the presence of one-tenth micromolar HgCl2-Ringer.